Patients diagnosed with Glioblastoma multiforme (GBM) only survive a median time of sixteen (16) months through extensive neurosurgery and chemotherapy along with radiation therapy. Research has demonstrated that within a timeframe of five (5) days HNSCs are able to migrate next to the brain tumors in mice. Therefore, it may be concluded that the tumor itself along with surrounding tissue should contain an abundant amount of HNSCs. Integrating this knowledge, a novel GBM therapy may be devised. The long range goal is to remove tumors from GBM patients, isolate the patient's Human Neural Stem Cells (HNSCs), transfect them with the PEX gene within a mammalian expression vector and then transplant the patients original HNSCs back into the brain. PEX is part of the C-terminal fragment of MMP2 metalloproteinase shown to prevent “normal biding to alpha-V/beta-3 and disrupts angiogenesis and tumor growth”. The central hypothesis is that after transfection of the patients HNSCs with the PEX gene, the cells will migrate to the site of tumor cells, express PEX and inhibit tumor growth and possibly promote apoptosis. The objectives of this project would be to achieve the following aims: AIM 1. Optimize a highly effective method for selecting all three (3) types of cells from a brain tumor sample. (Cancer Stem Cells, GBM Tumor Cells, Human Neural Stem Cells) AIM 2. To determine whether human neural stem cells transfected with the PEX gene effectively kill the tumor cells in vitro. AIM 3. To investigate whether PEX transfected HNSCs eliminate human tumor cells in vivo through mouse models. Aim 4. Perform clinical tests to determine whether PEX transfected HNSCs eliminate tumor cells in the patient. This proposed research is innovative, because it focuses on isolating Human Neural Stem Cells directly from tumor patient samples and transfecting them with an anti-cancerous gene such as PEX. This research is expected to have the following outcomes: (1) Isolation of all three types of the cells from patients' brain tumor samples; (2) demonstration that PEX transfected HNSCs will effectively inhibit tumor growth in-vitro and in-vivo; and (3) demonstration of elimination of GBM in patients using their own HNSCs expressing PEX. This research is significant because it will provide a novel GBM therapy using the patient's own HNSCs.
A present challenge in the treatment of glioblastoma multiforme is the fact that patients diagnosed with this disease rarely undergo surgery which effectively removes all carcinoma cells from the site of the lesion. Therefore a solution to this problem may be devised through isolation of Human Neural Stem Cells in the patient's own tumor. Through this effort we can use the patients HNSCs as therapy for the patient thus eliminating any possible chance of immunorejection from the patient.